1. Field of the Invention
The invention relates to highly active and stable ruthenium metal carbene complex compounds and their use as catalysts for olefin metathesis reactions.
2. Description of the Related Art
The formation of carbon-carbon bonds via olefin metathesis is of considerable interest and commercial utility, and considerable research efforts have been undertaken to develop olefin metathesis catalysts and systems. Group VIII transition metal catalysts have proven to be particularly useful for catalyzing olefin metathesis reactions, such as ring-opening metathesis polymerization (ROMP), ring-closing metathesis polymerization (RCM), acyclic diene metathesis (ADMFT), and cross metathesis reactions. Both classical and well-defined olefin metathesis catalysts based on ruthenium have been shown to exhibit good tolerance to a variety of functional groups, as has been reported by, e.g., Grubbs, R. H. J. M. S.-Pure Appl. Chem. 1994, A31(11), 1829-1833; Aqueous Organometallic Chemistry and Catalysis. Horvath, I. T., Joo, F. Eds; Kluwer Academic Publishers: Boston, 1995; Novak, B. M.; Grubbs, R. H. J. Am. Chem. Soc. 1988, 110, 7542-7543; Novak, B. M.; Grubbs, R. H. J. Am. Chem. Soc. 1988, 110, 960-96; Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H. J. Am. Chem. Soc. 1992, 114, 3974-3975 and Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996, 118, 100, each of which is incorporated herein by reference. In particular, as reported by Lynn, D. M.; Kanaoka, S.; Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 784 and by Mohr, B.; Lynn, D. M.; Grubbs, R. H. Organometallics 1996, 15, 4317-4325, both of which are incorporated herein by reference, the robust nature of the ruthenium-carbon bonds in these complexes has enabled olefin metathesis reactions to be carried out in protic media. However, slow reaction rates and low yields have limited the application of these catalysts for a variety of olefin monomers and reaction conditions.
As an example, there is a need for homogeneous polymerization systems that are living in water and that will polymerize water-soluble monomers. In living polymerization systems, polymerization occurs without chain transfer or chain termination, giving greater control over polydispersity of the resultant polymers. Such polymerization systems are highly desirable as they would allow the controlled synthesis of water-soluble polymers and would enable precise control over the composition of block copolymers for use, for example, in biomedical applications. However, such polymerization systems represent a formidable challenge. For example, the addition of water to traditional living anionic or cationic systems results in rapid termination. The advent of late transition metal catalysts tolerant of numerous polar and protic functionalities has recently enabled living ring-opening metathesis polymerizations (ROMP), free-radical polymerizations, and isocyanide polymerizations in aqueous environments, as reported by Lynn, D. M.; Kanaoka, S.; Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 784; Manning, D. D.; Strong, L. E.; Hu, X.; Beck, P.; Kiessling, L. L. Tetrahedron, 1997, 53, 11937-11952; Manning, D. D.; Hu, X.; Beck, P.; Kiessling, L. L. J.Am. Chem. Soc. 1997, 119, 3161-3162; Nishikawa, T; Ando, T; Kamigaito, M; Sawamoto, M. Macromolecules 1997, 30, 2244-2248; Deming, T. J.; Novak, B. M. Polym. Prepr. (Am. Chem. Soc., Div. Polym. Chem.) 1991, 32, 455-456; and Deming, T. J.; Novak, B. M. Macromolecules, 1991, 24, 326-328, each of which is incorporated herein by reference. Although these examples represent significant advances toward entirely aqueous systems, the catalysts themselves are insoluble in water and the polymerization reactions basically occur in xe2x80x9cwetxe2x80x9d organic phases.
Aqueous ring-opening metathesis polymerization of strained, cyclic olefins initiated by Group VIII salts and coordination complexes is well-documented. Although these complexes serve as robust polymerization catalysts in water, the polymerizations are not living and inefficient initiation steps produce erratic results (typically less than 1% of metal centers are converted to catalytically-active species) and results in poor control over polymer molecular weight.
We recently reported the synthesis of well-defined, water soluble ruthenium alkylidenes which serve as excellent initiators for olefin metathesis reactions in water, methanol, and aqueous emulsions. See Mohr, B.; Lynn, D. M.; Grubbs, R. H. Organometallics, 1996, 15, 4317-4325, incorporated herein by reference. Further investigation of these complexes, however, revealed that potential applications could be limited by relatively fast termination reactions. Similar ruthenium alkylidene complexes are disclosed in U.S. Pat. Nos. 5,312,940 and 5,342,909 and U.S. application Ser. No. 08/693,789, filed Jul. 31, 1996 (now U.S. Pat. No. 5,831,100), and Ser. No. 08/708,057, filed Aug. 30, 1996 (now U.S. Pat. No. 5,710,290), each of which is incorporated herein by reference.
For these reasons, there is a need for well-defined olefin metathesis catalysts and systems with improved efficiencies that provide for increased reaction rates, increased product yields, and that allow for metathesis of a wider range of olefins in a broader range of solvents than previously possible.
The present invention meets the above and other needs and is directed to the use of acid to activate and enhance ruthenium-based metathesis catalysts for olefin metathesis, including ring-opening metathesis polymerization (ROMP) of strained and unstrained cyclic olefins, and ring-closing metathesis (RCM), acyclic diene metathesis (ADMET), and cross metathesis reactions of acyclic olefins.
In one embodiment of the invention, the ruthenium catalyst compounds are ruthenium carbene complexes of the general formula AxLyXzRuxe2x95x90CHRxe2x80x2 where x=0, 1 or 2, y=0, 1 or 2, and z=1 or 2, and where Rxe2x80x2 is hydrogen or a substituted or unsubstituted alkyl or aryl, L is any neutral electron donor, X is any anionic ligand, and A is a ligand. having a covalent structure connecting a neutral electron donor and an anionic ligand. In other embodiments of the invention, the ruthenium catalyst compounds have the general formulas:
A2LRuxe2x95x90CHRxe2x80x2, ALXRuxe2x95x90CHRxe2x80x2 and L2X2Ruxe2x95x90CHRxe2x80x2.
These ruthenium catalysts contain acid-labile ligands and the addition of inorganic or organic acids to olefin metathesis reactions employing these catalysts results in substantially enhanced activities relative to systems in which acid is not present. Substantial rate increases in the presence of acid have been observed for olefin metathesis reactions in aqueous, protic and organic solvents in methods according to the present invention.
In another aspect of the invention, acid is used to activate ruthenium alkylidene complexes that are otherwise unreactive with olefins. This aspect of the invention allows for greater control in reaction injection molding (RIM) processes, as the catalyst and monomer can be stored together, either in solution or in neat monomer, and then acid is added to initiate polymerization. Similar processes can be applied to photoinitiated-ROMP (PROMP) systems and to photomasking applications using photoacid generators (photoacid generators are compounds that are not themselves acids, but which break down into acids and other products upon exposure to light energy).
The invention is further directed to living polymerization reactions taking place in aqueous solutions in the absence of any surfactants or organic cosolvents. In another embodiment of the invention, water-soluble ruthenium alkylidene complexes initiate living ROMP of water-soluble monomers in the presence of acid.
In general, transition metal alkylidenes are deactivated or destroyed in polar, protic species. The ruthenium alkylidenes of the present invention are not only stable in the presence of polar or protic functional groups or solvents, but the catalytic activities of these alkylidenes are enhanced by the deliberate addition of specific amounts of acid not present as a substrate or solvent. A number of ruthenium alkylidenes of the present invention are otherwise inactive absent the addition of acid to the reaction mixture. Such acidic conditions would destroy alkylidenes based on earlier transition metals.
Ruthenium alkylidenes of the present invention include alkylidenes of the general formula AxLyXzRuxe2x95x90CHRxe2x80x2 where x=0, 1 or 2, y=0, 1 or 2, and z=1 or 2, and where Rxe2x80x2 is hydrogen or a substituted or unsubstituted alkyl or aryl, L is any neutral electron donor, X is any anionic ligand, and A is a ligand having a covalent structure connecting a neutral electron donor and an anionic ligand. These alkylidenes have enhanced catalytic activities in the presence of acid for a variety of olefin metathesis reactions, including but not limited to ROMP, RCM, ADMET and cross-metathesis and dimerization reactions. Preferred ruthenium alkylidenes are of the general formulas A2LRuxe2x95x90CHRxe2x80x2, ALXRuxe2x95x90CHRxe2x80x2 and L2X2Ruxe2x95x90CHRxe2x80x2.
Olefin monomers that can be reacted according to the processes of the present invention include acyclic olefins, cyclic olefins, both strained and unstrained, dienes and unsaturated polymers. These olefins can be functionalized as well, and can include functional groups either as substituents of the olefins or incorporated into the carbon chain of the olefin. These functional groups can be, for example, alcohol, thiol, ketone, aldehyde, ester, disulfide, carbonate, imine, carboxyl, amine, amide, nitro acid, carboxylic acid. isocyanate, carbodiimide, ether, halogen, quaternary amine, carbohydrate, phosphate, sulfate or sulfonate groups.
Both organic and inorganic acids are useful in enhancing catalytic activity of our catalysts, the preferred acids being HI, HCl, HBr, H2SO4, H3O+, HNO3, H3PO4, CH3CO2H and tosic acid, most preferably HCl. Acids may be added to the catalysts either before or during the reaction with olefin, with longer catalyst life generally observed when the catalyst is introduced to an acidic solution of olefin monomer. The acid or the catalyst can be dissolved in a variety of suitable solvents, including protic, aqueous or organic solvents or mixtures thereof. Preferred solvents include aromatic or halogenated aromatic solvents, aliphatic or halogenated organic solvents, alcoholic solvents, water or mixtures thereof. Of the aromatic solvents, the most preferred is benzene. Dichloromethane is most preferred of the halogenated aliphatic solvents; methanol is most preferred of the alcoholic solvents. Alternatively, the acid or the catalyst or both can be dissolved into neat olefin monomer.
In addition to the above acids, an alternative embodiment of the invention, photoacid generators that are converted to acids upon exposure to light energy may be used to activate or enhance the reaction. For example, UV curing of dicyclopentadiene (DCPD) to yield poly(DCPD) by photoinitiated-ROMP (PROMP) is readily accomplished as photoacid generators may be stored with both monomer and catalyst until metathesis is initiated through irradiation.
The preferred substituents of catalysts of the present invention are as follows. The neutral electron donor L is preferably a phosphine of the formula PR3R4R5 where R3 can be a secondary alkyl or cycloalkyl, and R4 and R5 can be an aryl, C1-C10 primary alkyl, secondary alkyl, or cycloalkyl, each independent of the other. More preferably, L is either P(cyclohexyl)3, P(cyclopentyl)3, P(isopropyl)3, or P(phenyl)3. The anionic ligand X is preferably hydrogen, or a halogen, or a unsubstituted or substitued moiety where the moiety is a C1-C20 alkyl, aryl, C1-C20 alkoxide, aryloxide, C3-C20 alkyldiketonate, aryldiketonate, C1-C20 carboxylate, arylsulfonate, C1-C20 alkylsulfonate, C1-C20 alkylthio, C1-C20 alkylsulfonyl, or C1-C20 alkylsulfinyl. In the case of substituted moiety, the substitution is C1-C5 alkyl, halogen, C1-C5 alkoxy, unmodified phenyl, halogen substituted phenyl, C1-C5 alkyl substituted phenyl, or C1-C5 alkoxy substituted phenyl.
A first preferred embodiment of the catalyst has the formula: 
where each R is an aryl or alkyl, substituted or unsubstituted, and is preferably either a C1-C20 alkyl, an aryl, a substituted C1-C20 alkyl (substituted with an aryl, halide, hydroxy, C1-C20 alkoxy, or C2-C20 alkoxycarbonyl) or a substituted aryl (substituted with a C1-C20 alkyl, aryl, hydroxyl, C1-C5 alkoxy, amino, nitro, halide or methoxy). In the most preferred form, R is methyl or t-butyl, PR3 is P(cyclohexyl)3 and Rxe2x80x2 is phenyl.
A second preferred embodiment of the catalyst has the formula: 
where Rxe2x80x3 is hydrogen, alkyl, halo, nitro or alkoxy, X is Cl, Br, I, CH3CO2 or CF3CO2 and each R is a substituted or unsubstituted alkyl or aryl, preferably either a C1-C20 alkyl, an aryl, a substituted C1-C20 alkyl (substituted with an aryl, halide, hydroxy, C1-C20 alkoxy, or C2-C20 alkoxycarbonyl) or a substituted aryl (substituted with a C1-C20 alkyl, aryl, hydroxyl, C1-C5 alkoxy, amino, nitro, halide or methoxy). In the most preferred form, Rxe2x80x2 is phenyl, Rxe2x80x3 is nitro, PR3 is P(cyclohexyl)3, X is Cl and R is aryl or aryl substituted with 2,6-diisopropyl groups.
A third preferred embodiment of the catalyst has the formula: 
where PR3 is either P(cyclohexyl)3, P(cyclopentyl)3, P(isopropyl)3, or P(phenyl)3 and X is Cl, Br, I, CH3CO2 or CF3CO2.
A fourth preferred embodiment of the catalyst has the formula: 
where Cy is cyclohexyl, X is Cl, Br, I, CH3CO2 or CF3CO2, and R is one of the following: 
Preferred forms of this fourth embodiment have the following formulas: 
The catalysts of this fourth embodiment are highly effective when used in either aqueous or alcoholic solvents.
The ruthenium alkylidene compounds of the present invention may be synthesized using diazo compounds, by neutral electron donor ligand exchange, by cross metathesis, using acetylene, using cumulated olefins, and in a one-pot method using diazo compounds and neutral electron donors according to methods described in U.S. Pat. Nos. 5,312,940 and 5,342,909 and U.S. application Ser. No. 08/693,789, filed Jul. 31, 1996, and Ser. No. 08/708,057, filed Aug. 30, 1996 (issued U.S. Pat. Nos. 5,831,108 and 5,710,298, respectively) and in Chang, S., Jones, L., II, Wang, C., Henling, L. M., and Grubbs, R. H., Organometallics, 1998, 17, 3460-3465, Schwab, P., Grubbs, R. H., Ziller, J. W., J. Am. Chem. Soc. 1996, 118, 100-110, and Mohr, B., Lynn, D. M., and Grubbs, R. H., Organometallics, 1996, 15, 4317-4325, each of which is incorporated herein by reference in its entirety, and to methods further described herein.